The Problem Of Infection Xenozoonoses

Although progress has been made in solving the immunologic problems of pig-to-human xenografting, concerns have been increasingly raised regarding the infectious disease potential of xenotransplantation. The use of organs of nonhuman origin would greatly expand the spectrum of potential infectious diseases presently encountered in clinical transplantation to include those pathogens derived from other animal species. Not suprisingly, concerns have been raised over the potential for the introduction of zoonotic diseases not only into the transplant recipient, but into the general human population. Although known infectious pathogens of a donor species can be easily monitored and very likely eliminated through controlled breeding of pathogen-free herds, there may exist novel, latent pathogens capable of inducing symptomatic disease in the xenograft recipient. Retroviruses represent such agents.

Many mammalian species possess retroviruses integrated into their cellular DNA, so-called endogenous retroviruses. These retroviruses are capable of replication and transmission to cells of a different species, and have the potential to cause disease if so transmitted. Endogenous retroviruses have been linked to development of cancers. Recently, pig endogenous retrovirus (PERV) has been shown to infect human cells. This observation raises serious questions regarding the short and long-term risks of xenotransplantation.

Available data suggest the PERV possesses zoonotic potential for human cells in vitro. Replication-competent PERV has been demonstrated in a variety of pig cells and tissues, including peripheral blood mononuclear cells, endothelial cells, islets, and hepatocytes. In addition, different subtypes of PERV, with possible differences in tissue tropisms, have been identified.

There are many unanswered questions regarding PERV. While in vitro infection of human cells by PERV has been demonstrated, an exhaustive review of humans with acute and long-term exposure to porcine tissues, including porcine extracorporeal hepatic assist devices, has failed to demonstrate PERV infection of humans. Although these data are encouraging, they are potentially misleading: the risk of infection in a heavily immunosuppressed recipient of an immediately vascularized

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